System and Method For Quality Assurance in Pathology

ABSTRACT

Enhancing color(s) in a digital slide image to increase contrast. In an embodiment, a digital slide image of a tissue sample is acquired. The tissue sample is counterstained, such that the digital slide image comprises an image of a first stain and a second stain. The contrast between the first stain and the second stain is increased to enhance the digital slide image.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 14/330,844, filed on Jul. 14, 2014, which is a continuation ofU.S. patent application Ser. No. 14/065,708, filed on Oct. 29, 2013 andissued as U.S. Pat. No. 8,885,900, which is a continuation of U.S.patent application Ser. No. 13/453,767, filed on Apr. 23, 2012 andissued as U.S. Pat. No. 8,571,286, which is a continuation of U.S.patent application Ser. No. 12/114,627, filed on May 2, 2008 and issuedas U.S. Pat. No. 8,165,363, which claims priority to U.S. ProvisionalPatent App. No. 60/916,252, filed on May 4, 2007, all of which arehereby incorporated herein by reference in their entireties.

BACKGROUND

1. Field of the Invention

The present invention generally relates to pathology and microscopy andmore particularly relates to improvements in quality assurance forpathology using digital microscopy.

2. Related Art

The diagnosis of glass microscope slides by a pathologist is known to besubjective. Many factors contribute to this lack of objectivity,including the training and skill of the pathologist and the quality ofthe glass slides from which the diagnosis was made. While use of tissueprocessing instruments and automatic staining equipment has increasedthe quality and consistency of slide preparations, a significant portionof glass slides that are read by pathologists are still suboptimal andmay contribute to inaccurate interpretations.

One of the possible contributing factors to the subjectivity of readingpathology slides is the lack of standardization of the microscope, atool that has been in use for hundreds of years and which is notrecognized as an approved medical device. Pathologists are free to usewhatever microscope they want to read glass slides and are expected toknow how to keep their microscope in optimal (Koehler) alignment, whatobjectives lenses with what numerical apertures are best suited fordifferent specimen types, and to be aware when the bulb in theirmicroscope needs to be replaced (because the color temperature of theilluminating light will change the color in the image they observethrough the microscope). Many pathologists' microscopes are notmaintained in optimal working condition or furnished with optimalobjective lenses, thus compromising spatial details and color fidelitythat may be essential to making more accurate diagnoses.

Another likely contributing factor to the subjectivity of pathology isdeficiencies in glass slide quality, which can include over- orunder-staining (i.e., too dark or too light), tissue folds, sectionsthat are too thick or too thin, bubbles, debris as well as variations inimage quality observed between slides prepared by differentautostainers. There is little a pathologist can do to overcome thechallenges of a poorly prepared glass slides (“garbage in/garbage out”),other than to try to make adjustments in the optical properties of themicroscope (adjust condenser, increase/decrease light) to try andameliorate glass slide quality problems.

Referring to FIG. 1, a flow diagram illustrating a conventional processfor quality assurance using glass slides is shown. Initially, in step100 a glass slide is prepared and then in step 110 the quality of theslide is inspected and assessed. In a typical laboratory, ahistotechnologist screens the glass slides to assess slide quality, asshown in step 120, and rejects sub-optimal slides before they are readby a pathologist. Rejected slides result in re-cuts and the preparationof new, presumably higher quality, glass slides. In some cases, theslides can be fixed, e.g., by restaining if the staining is too light.This is shown in step 130. Finally, when a glass slide is acceptable,the slide is reviewed and interpreted by a pathologist in step 140.

This conventional process suffers from the inability of thehistotechnologist to carefully review every area of a glass slide (somelabs process hundreds or thousands of slides every day). Theconventional process additionally suffers from the increasing shortageof qualified histotechnologists, and pressure on laboratories tocontinually improve productivity. Furthermore, the overall aging of thepopulation and the associated increased incidence of cancer (andsurgical biopsies) only exacerbate the challenges of quality-assuringglass slides before they are read by a pathologist due to thesignificant increase in the number of glass slides that are prepared.

Therefore, what is needed is a system and method that overcomes thesesignificant problems found in the conventional systems as describedabove.

SUMMARY

Accordingly, described herein are systems and methods for improvingquality assurance in pathology using digital slide tools for assessingslide quality to trigger (i) preparation of new glass slides, (ii)re-scanning of glass slides, or (iii) enhancement of digital slidesprior to interpretation by the pathologist. Digital slides created byslide scanning instruments contribute to improved diagnosis bypathologists by providing an automatic, systematic, objective, andconsistent means for digital slide creation and analysis, enabling theuse of computer implemented image analysis and image correction tools.

A digital pathology system (slide scanning instrument and software)assesses and improves the quality of a digital slide. The improveddigital slide has a higher image quality that results in increasedefficiency in the interpretation of such digital slides when they areviewed on a monitor by a pathologist. These improved digital slidesyield a more objective diagnosis than reading the corresponding glassslide under a microscope.

Other features and advantages of the present invention will become morereadily apparent to those of ordinary skill in the art after reviewingthe following detailed description and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The details of the present invention, both as to its structure andoperation, may be gleaned in part by study of the accompanying drawings,in which like reference numerals refer to like parts, and in which:

FIG. 1 is a flow diagram illustrating a conventional process for qualityassurance using glass slides;

FIG. 2 is a flow diagram illustrating a process for quality assuranceusing digital slides according to an embodiment of the invention;

FIG. 3 is a flow diagram illustrating an alternative process for qualityassurance using digital slides according to an embodiment of theinvention;

FIG. 4 is a flow diagram illustrating an alternative process for qualityassurance using digital slides according to an embodiment of theinvention;

FIG. 5 is a network diagram illustrating a digital pathology system forimproved quality assurance in pathology according to an embodiment ofthe invention; and

FIG. 6 is a block diagram illustrating an example computer system thatmay be used in connection with various embodiments described herein.

DETAILED DESCRIPTION

Certain embodiments as disclosed herein provide for systems and methodsfor quality assurance in pathology. After reading this description itwill become apparent to one skilled in the art how to implement theinvention in various alternative embodiments and alternativeapplications. However, although various embodiments of the presentinvention will be described herein, it is understood that theseembodiments are presented by way of example only, and not limitation. Assuch, this detailed description of various alternative embodimentsshould not be construed to limit the scope or breadth of the presentinvention as set forth in the appended claims.

FIG. 2 is a flow diagram illustrating a process for quality assuranceusing digital slides according to an embodiment of the invention. Theillustrated process can be carried out by a digital pathology systemsuch as that later described with respect to FIG. 5. Initially, in step200 the glass slide is prepared in the conventional manner. Next, instep 210 the glass slide is scanned (digitized) to create a high qualitydigital slide image of the glass slide at a diagnostic resolution forthe tissue type. Once the digital slide is created, computer implementeddigital slide analysis tools are automatically applied to the slide instep 220 to assess the quality of the digital slide image. For example,the color and focus of a digital slide can be analyzed by qualitymodules that consider image attributes that include the contrast,brightness and spatial resolution of individual and groups of pixels inthe digital slide image. If the quality of the digital slide isinsufficient, as determined in step 230, the corresponding glass slidecan be rejected and an operator can prepare a new glass slide. If thequality of the digital slide is sufficient for diagnosis, as determinedin step 230, then the digital slide can be analyzed and interpreted by apathologist, who views the digital slide on the monitor at a local orremote viewing station. Alternatively, glass slides in which the qualityof the corresponding digital slide is determined to be sufficient by thecomputer implemented digital slide analysis tools, could be interpretedby a pathologist using a microscope.

In one embodiment, the digital slide quality assessment is made bycomparing objective characteristics of the digital slide against apredetermined set of criteria. Advantageously, this provides aconsistent and standard level of quality in any digital slide image thatcan be systematically applied to all digital slides destined for reviewby a pathologist.

Additionally, in one embodiment the digitizing and automatic assessmentof the digital slide may be employed for the sole purpose of removingthis task from the histotechnologist, thereby allowing that person toperform other tasks and improve efficiencies. In such an embodiment, thehistologist may be notified of borderline quality slides in order tomake the final determination of quality for a significantly fewer numberof glass slides.

FIG. 3 is a flow diagram illustrating an alternative process for qualityassurance using digital slides according to an embodiment of theinvention. The illustrated process can be carried out by a digitalpathology system such as that later described with respect to FIG. 5.The process in FIG. 3 is initially similar to the process described withrespect to FIG. 2 so only the differences will be described here.

Once the glass slide is prepared and digitized and analyzed by thedigital slide analysis tools and quality modules, if the quality of thedigital slide is insufficient, as determined in step 330, the digitalslide image can be rejected and an operator can rescan the glass slide.This can be more efficient if, for example, the digital slide image wasrejected due to problems with focus or even problems with too muchstaining. In one embodiment, a rescan of a glass slide with too muchstaining can be done with decreased light during scanning in order toaccount for the over staining. Advantageously, this saves significanttime in the overall process and also saves the native tissue source andother goods used in glass slide preparation.

Once a digital image of sufficient quality is created, as determined instep 330, the system next applies computer implemented digital slideenhancement tools to improve the quality of the digital slide image evenfurther, as shown in step 340. For example, the colors of stains can beenhanced or even changed to provide more color contrast incounterstained samples. After the quality assured and image enhanceddigital slide is ready, then in step 350 the digital slide can beanalyzed and interpreted by a pathologist, who views the digital slideon the monitor at a local or remote reviewing station.

In one embodiment, when a digital slide meets the predetermined qualitycriteria and is then improved by computer implemented digitalenhancement, the improved digital slide is fed into a clinical decisionsupport system that guides the pathologist through the process of makingan interpreting the slide in order to arrive at a diagnosis for theslide, or the case associated with the slide.

A few variations in the process shown in FIG. 3 are also possible. Forexample, if the image quality of the digital slide as determined in step320 is poor then a new glass slide maybe prepared rather than rescanningthe original glass slide. Additionally, providing digital enhancementsto the digital slide image is not a necessary step in the processalthough it provides potentially significantly improved images and canfacilitate a more accurate diagnosis by the pathologist.

In one embodiment, the quality assurance system described hereinincludes using the slide scanning instrument to assess the quality ofthe glass slide being scanned, and in the event that the glass slidefails predetermined quality criteria, the scanning parameters of thescanning instrument are modified to create a digital slide with improvedquality. For example, a slide that is over stained (too dark) would beautomatically re-scanned with less light. The determination of whetherthe glass slide meets predetermined quality criteria can be achieved byinitially scanning the glass slide at low or high power and thenperforming certain types of image analysis on the resulting image todetermine, as in the above example, if the slide is too dark.

FIG. 4 is a flow diagram illustrating an alternative process for qualityassurance using digital slides according to an embodiment of theinvention. The illustrated process can be carried out by a digitalpathology system such as that later described with respect to FIG. 5.Initially, in step 400 a glass slide is digitized and then in step 410the digital slide is automatically evaluated against a set ofpredetermined criteria to assess the digital slide quality. In step 420,slides that meet or exceed the objective baseline for digital slidequality are then digitally enhanced where possible and then the digitalslide is provided to a pathologist for review and analysis, as shown instep 430.

Advantageously, the embodiment shown in FIG. 4 is a highly streamlinedcomputer implemented process. A plurality of slides may be provided tothe digital microscopy system for automatic serial or parallel scanningthat results in the digital slides being provided to a local or remotepathologist for analysis and diagnosis.

In one embodiment, examples of the types of enhancements made in step420 to improve the digital slide image prior to diagnosis by apathologist include enhancement of contrast, color, elimination ofdefects, and the like including other image processing techniques.

For example, color space standardization can be used to transform thedigital slide image into a standardized or non-standardized (and better)color space. Doing so can ensure that digital slides displayed on amonitor appear more consistent in color than the corresponding glassslides would appear under a microscope. Additionally, image processingcan apply image enhancement filters (e.g., sharpening, deconvolution,etc.) to the digital slide to enhance spatial details that are notreadily apparent to the naked eye. Also, quality assessments can becomputed to provide the pathologist an objective computer-generatedmeasure of digital slide quality that informs the pathologist about theunderlying integrity of the digital slide. This can be particularlyadvantageous to a pathologist because knowing that the digital slidequality is suboptimal (e.g., because of poor sample preparation) can behelpful to a pathologist. For example, if the result of a diagnosis of asuboptimal digital slide required surgery, the pathologist may insteadorder a new glass slide to be prepared and digitized in order to conducta second review and analysis of the tissue.

Image pattern recognition can also be employed, for example, as part ofa decision support system, to automatically identify for a pathologistthose regions of a digital slide which have diagnostic significance.This can be very helpful and provide a pathologist with the ability tointerrogate regions of one or more digital slides in priority order.Additionally, content based image retrieval can be extremely useful byproviding the pathologist with previously diagnosed (i.e., “solved”cases) that have similar image patterns to the digital slide beinganalyzed. In one embodiment, a database of digital slides or otherimages can be accessed to retrieve digital slides or other images thatshow characteristics similar to the digital slide under review.

FIG. 5 is a network diagram illustrating a digital pathology system 500for improved quality assurance in pathology according to an embodimentof the invention. In the illustrated embodiment, the system 500comprises a slide scanner 510 that is communicatively coupled with aslide reviewer station 520 via a network 530.

The slide scanner 510 can be any of a variety of digital slide creationsystems including image tiling systems, array scanning systems, or linescanning systems, including line scanning systems utilizingtime-delay-integration (“TDI”). The line scanning systems are preferredbecause they create digital slides more rapidly and also because theresulting digital slide images have a much higher quality both in termsof better focus and reduced artifacts such as stitching that aretypically introduced by image tiling systems.

The slide scanner functions to digitize a glass slide and store thedigital slide in the data storage area 515. Also stored in the datastorage area 515 are digital slide analysis tools and modules that canbe implemented by the slide scanner 510 to assess the quality of adigital slide. Additionally, digital slide enhancement tools and modulesthat can be implemented by the slide scanner 510 to improve the qualityof a digital slide are also stored in the data storage area 515. Theseanalysis and enhancement tools may also be stored in a separate local orremote data storage area (not shown), for example to conserve processorpower at the scanning station and to allow another device to perform theanalysis and enhancement functions.

The slide reviewer station 520 can be in communication with the slidescanner 510 either directly (not shown) or via the network 530, whichmay be a local or wide area network, public or private network, and mayor may not include that global combination of networks that is commonlyknown as the Internet. The slide reviewer station 520 is configured withits own data storage area 525 and allows a pathologist or other analyst(e.g., histotechnologist) to review digital slides that are stored atthe slide scanner 510 or at the slide reviewer station 520.

In one embodiment, slides are digitally scanned, their image quality isassessed and slides with sufficient quality are digitally enhanced andthen subsequently sent via a network to the reviewing station of apathologist for analysis. This entire process can be automated, forexample by the presence of a barcode on the glass slide that providesinformation about where the send the enhanced digital slide image foranalysis by the pathologist.

FIG. 6 is a block diagram illustrating an example computer system 550that may be used in connection with various embodiments describedherein. For example, the computer system 550 may be used in conjunctionwith the slide scanner system or slide reviewer system previouslydescribed with respect to FIG. 5. Other computer systems and/orarchitectures may also be used, as will be clear to those skilled in theart.

The computer system 550 preferably includes one or more processors, suchas processor 552. Additional processors may be provided, such as anauxiliary processor to manage input/output, an auxiliary processor toperform floating point mathematical operations, a special-purposemicroprocessor having an architecture suitable for fast execution ofsignal processing algorithms (e.g., digital signal processor), a slaveprocessor subordinate to the main processing system (e.g., back-endprocessor), an additional microprocessor or controller for dual ormultiple processor systems, or a coprocessor. Such auxiliary processorsmay be discrete processors or may be integrated with the processor 552.

The processor 552 is preferably connected to a communication bus 554.The communication bus 554 may include a data channel for facilitatinginformation transfer between storage and other peripheral components ofthe computer system 550. The communication bus 554 further may provide aset of signals used for communication with the processor 552, includinga data bus, address bus, and control bus (not shown). The communicationbus 554 may comprise any standard or non-standard bus architecture suchas, for example, bus architectures compliant with industry standardarchitecture (“ISA”), extended industry standard architecture (“EISA”),Micro Channel Architecture (“MCA”), peripheral component interconnect(“PCI”) local bus, or standards promulgated by the Institute ofElectrical and Electronics Engineers (“IEEE”) including IEEE 488general-purpose interface bus (“GPIB”), IEEE 696/S-100, and the like.

Computer system 550 preferably includes a main memory 556 and may alsoinclude a secondary memory 558. The main memory 556 provides storage ofinstructions and data for programs executing on the processor 552. Themain memory 556 is typically semiconductor-based memory such as dynamicrandom access memory (“DRAM”) and/or static random access memory(“SRAM”). Other semiconductor-based memory types include, for example,synchronous dynamic random access memory (“SDRAM”), Rambus dynamicrandom access memory (“RDRAM”), ferroelectric random access memory(“FRAM”), and the like, including read only memory (“ROM”).

The secondary memory 558 may optionally include a hard disk drive 560and/or a removable storage drive 562, for example a floppy disk drive, amagnetic tape drive, a compact disc (“CD”) drive, a digital versatiledisc (“DVD”) drive, etc. The removable storage drive 562 reads fromand/or writes to a removable storage medium 564 in a well-known manner.Removable storage medium 564 may be, for example, a floppy disk,magnetic tape, CD, DVD, etc.

The removable storage medium 564 is preferably a computer readablemedium having stored thereon computer executable code (i.e., software)and/or data. The computer software or data stored on the removablestorage medium 564 is read into the computer system 550 as electricalcommunication signals 578.

In alternative embodiments, secondary memory 558 may include othersimilar means for allowing computer programs or other data orinstructions to be loaded into the computer system 550. Such means mayinclude, for example, an external storage medium 572 and an interface570. Examples of external storage medium 572 may include an externalhard disk drive or an external optical drive, or and externalmagneto-optical drive.

Other examples of secondary memory 558 may include semiconductor-basedmemory such as programmable read-only memory (“PROM”), erasableprogrammable read-only memory (“EPROM”), electrically erasable read-onlymemory (“EEPROM”), or flash memory (block oriented memory similar toEEPROM). Also included are any other removable storage units 572 andinterfaces 570, which allow software and data to be transferred from theremovable storage unit 572 to the computer system 550.

Computer system 550 may also include a communication interface 574. Thecommunication interface 574 allows software and data to be transferredbetween computer system 550 and external devices (e.g. printers),networks, or information sources. For example, computer software orexecutable code may be transferred to computer system 550 from a networkserver via communication interface 574. Examples of communicationinterface 574 include a modem, a network interface card (“NIC”), acommunications port, a PCMCIA slot and card, an infrared interface, andan IEEE 1394 fire-wire, just to name a few.

Communication interface 574 preferably implements industry promulgatedprotocol standards, such as Ethernet IEEE 802 standards, Fiber Channel,digital subscriber line (“DSL”), asynchronous digital subscriber line(“ADSL”), frame relay, asynchronous transfer mode (“ATM”), integrateddigital services network (“ISDN”), personal communications services(“PCS”), transmission control protocol/Internet protocol (“TCP/IP”),serial line Internet protocol/point to point protocol (“SLIP/PPP”), andso on, but may also implement customized or non-standard interfaceprotocols as well.

Software and data transferred via communication interface 574 aregenerally in the form of electrical communication signals 578. Thesesignals 578 are preferably provided to communication interface 574 via acommunication channel 576. Communication channel 576 carries signals 578and can be implemented using a variety of wired or wirelesscommunication means including wire or cable, fiber optics, conventionalphone line, cellular phone link, wireless data communication link, radiofrequency (RF) link, or infrared link, just to name a few.

Computer executable code (i.e., computer programs or software) is storedin the main memory 556 and/or the secondary memory 558. Computerprograms can also be received via communication interface 574 and storedin the main memory 556 and/or the secondary memory 558. Such computerprograms, when executed, enable the computer system 550 to perform thevarious functions of the present invention as previously described.

In this description, the term “computer readable medium” is used torefer to any media used to provide computer executable code (e.g.,software and computer programs) to the computer system 550. Examples ofthese media include main memory 556, secondary memory 558 (includinghard disk drive 560, removable storage medium 564, and external storagemedium 572), and any peripheral device communicatively coupled withcommunication interface 574 (including a network information server orother network device). These computer readable mediums are means forproviding executable code, programming instructions, and software to thecomputer system 550.

In an embodiment that is implemented using software, the software may bestored on a computer readable medium and loaded into computer system 550by way of removable storage drive 562, interface 570, or communicationinterface 574. In such an embodiment, the software is loaded into thecomputer system 550 in the form of electrical communication signals 578.The software, when executed by the processor 552, preferably causes theprocessor 552 to perform the inventive features and functions previouslydescribed herein.

Various embodiments may also be implemented primarily in hardware using,for example, components such as application specific integrated circuits(“ASICs”), or field programmable gate arrays (“FPGAs”). Implementationof a hardware state machine capable of performing the functionsdescribed herein will also be apparent to those skilled in the relevantart. Various embodiments may also be implemented using a combination ofboth hardware and software.

Furthermore, those of skill in the art will appreciate that the variousillustrative logical blocks, modules, circuits, and method stepsdescribed in connection with the above described figures and theembodiments disclosed herein can often be implemented as electronichardware, computer software, or combinations of both. To clearlyillustrate this interchangeability of hardware and software, variousillustrative components, blocks, modules, circuits, and steps have beendescribed above generally in terms of their functionality. Whether suchfunctionality is implemented as hardware or software depends upon theparticular application and design constraints imposed on the overallsystem. Skilled persons can implement the described functionality invarying ways for each particular application, but such implementationdecisions should not be interpreted as causing a departure from thescope of the invention. In addition, the grouping of functions within amodule, block, circuit or step is for ease of description. Specificfunctions or steps can be moved from one module, block or circuit toanother without departing from the invention.

Moreover, the various illustrative logical blocks, modules, and methodsdescribed in connection with the embodiments disclosed herein can beimplemented or performed with a general purpose processor, a digitalsignal processor (“DSP”), an ASIC, FPGA or other programmable logicdevice, discrete gate or transistor logic, discrete hardware components,or any combination thereof designed to perform the functions describedherein. A general-purpose processor can be a microprocessor, but in thealternative, the processor can be any processor, controller,microcontroller, or state machine. A processor can also be implementedas a combination of computing devices, for example, a combination of aDSP and a microprocessor, a plurality of microprocessors, one or moremicroprocessors in conjunction with a DSP core, or any other suchconfiguration.

Additionally, the steps of a method or algorithm described in connectionwith the embodiments disclosed herein can be embodied directly inhardware, in a software module executed by a processor, or in acombination of the two. A software module can reside in RAM memory,flash memory, ROM memory, EPROM memory, EEPROM memory, registers, harddisk, a removable disk, a CD-ROM, or any other form of storage mediumincluding a network storage medium. An exemplary storage medium can becoupled to the processor such the processor can read information from,and write information to, the storage medium. In the alternative, thestorage medium can be integral to the processor. The processor and thestorage medium can also reside in an ASIC.

The above description of the disclosed embodiments is provided to enableany person skilled in the art to make or use the invention. Variousmodifications to these embodiments will be readily apparent to thoseskilled in the art, and the generic principles described herein can beapplied to other embodiments without departing from the spirit or scopeof the invention. Thus, it is to be understood that the description anddrawings presented herein represent a presently preferred embodiment ofthe invention and are therefore representative of the subject matterwhich is broadly contemplated by the present invention. It is furtherunderstood that the scope of the present invention fully encompassesother embodiments that may become obvious to those skilled in the artand that the scope of the present invention is accordingly not limited.

1. A method comprising using at least one hardware processor to: acquirea digital slide image of a tissue sample that is counterstained with atleast a first stain and a second stain, such that the digital slideimage comprises an image of the first stain and the second stain; andincrease a contrast between the first stain and the second stain toenhance the digital slide image.
 2. The method of claim 1, whereinincreasing the contrast between the first stain and the second staincomprises changing a color of at least one of the first stain and thesecond stain.
 3. The method of claim 1, further comprising using the atleast one hardware processor to, prior to increasing the contrast,automatically determine whether or not a quality of the digital slideimage is sufficient for diagnosis.
 4. The method of claim 3, whereindetermining whether or not a quality of the digital slide image issufficient for diagnosis comprises comparing one or more characteristicsof the digital slide image to a predetermined set of one or morecriteria.
 5. The method of claim 3, wherein increasing the contrast isperformed automatically when the determination is that the quality ofthe digital slide image is sufficient.
 6. The method of claim 1, furthercomprising using the at least one hardware processor to input theenhanced digital slide image into a clinical decision support systemthat guides a user through an interpretation of the tissue sample toarrive at a diagnosis.
 7. A system comprising: at least one hardwareprocessor; and one or more software modules that, when executed by theat least one hardware processor, acquire a digital slide image of atissue sample that is counterstained with at least a first stain and asecond stain, such that the digital slide image comprises an image ofthe first stain and the second stain, and increase a contrast betweenthe first stain and the second stain to enhance the digital slide image.8. The system of claim 7, wherein increasing the contrast between thefirst stain and the second stain comprises changing a color of at leastone of the first stain and the second stain.
 9. The system of claim 7,wherein the one or more software modules, prior to increasing thecontrast, automatically determine whether or not a quality of thedigital slide image is sufficient for diagnosis.
 10. The system of claim9, wherein determining whether or not a quality of the digital slideimage is sufficient for diagnosis comprises comparing one or morecharacteristics of the digital slide image to a predetermined set of oneor more criteria.
 11. The system of claim 9, wherein the one or moresoftware modules increase the contrast automatically when thedetermination is that the quality of the digital slide image issufficient.
 12. The system of claim 7, wherein the one or more softwaremodules input the enhanced digital slide image into a clinical decisionsupport system that guides a user through an interpretation of thetissue sample to arrive at a diagnosis.
 13. The system of claim 7,wherein the at least one hardware processor is comprised in a slidescanner.
 14. The system of claim 13, wherein the one or more softwaremodules are stored in a memory of the slide scanner.
 15. Anon-transitory computer-readable medium having instructions storedthereon, wherein the instructions, when executed by a processor, causethe processor to: acquire a digital slide image of a tissue sample thatis counterstained with at least a first stain and a second stain, suchthat the digital slide image comprises an image of the first stain andthe second stain; and increase a contrast between the first stain andthe second stain to enhance the digital slide image.
 16. Thenon-transitory computer-readable medium of claim 15, wherein increasingthe contrast between the first stain and the second stain compriseschanging a color of at least one of the first stain and the secondstain.
 17. The non-transitory computer-readable medium of claim 15,wherein the instructions further cause the processor to, prior toincreasing the contrast, automatically determine whether or not aquality of the digital slide image is sufficient for diagnosis.
 18. Thenon-transitory computer-readable medium of claim 17, wherein determiningwhether or not a quality of the digital slide image is sufficient fordiagnosis comprises comparing one or more characteristics of the digitalslide image to a predetermined set of one or more criteria.
 19. Thenon-transitory computer-readable medium of claim 17, wherein theinstructions cause the processor to increase the contrast automaticallywhen the determination is that the quality of the digital slide image issufficient.
 20. The non-transitory computer-readable medium of claim 15,wherein the instructions further cause the processor to input theenhanced digital slide image into a clinical decision support systemthat guides a user through an interpretation of the tissue sample toarrive at a diagnosis.